The role of autophagy and HDAC6 in protein aggregate formation and clearance in oligodendrocytes

• Antragstellerin: Professorin Dr. Christiane Richter-Landsberg
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2010 bis 2015
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 183254749

The formation of protein aggregates containing the microtubule associated protein tau in neurons and glia is a common feature in a variety of neurodegenerative diseases termed tauopathies. In oligodendrocytes, the myelin forming cells of the CNS, tau fibrils accumulate as coiled bodies or glial cell inclusions. Cellular mechanisms for degrading abnormal or obsolete proteins include the ubiquitin-proteasome system (UPS) and autophagy, representing lysosome mediated degradative pathways. When the proteasomal system is unable to clear aggregates, autophagy may be the preferential route and act as a compensatory system. Autophagy plays a unique role in degrading and removing cellular organelles and protein aggregates that are too large to be degraded by the UPS. We want to investigate how autophagy is involved in the clearance of aggregated species of tau in oligodendroglial cells, and whether upregulation of autophagy ameliorates tau aggregate formation and has cell survival promoting consequences. A major goal of the proposed study is to elucidate to what extent the histone deacetylase 6 (HDAC6) is critically involved and a key element in autophagic degradation of tau in oligodendrocytes and contributes to pathogenesis.

• DFG-Verfahren: Sachbeihilfen